Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome

被引：30

作者：

Iannone, Luigi Francesco ^{[1
]}

Arena, Gabriele ^{[1
]}

Battaglia, Domenica ^{[2
]}

Bisulli, Francesca ^{[3
,4
]}

Bonanni, Paolo ^{[5
]}

Boni, Antonella ^{[3
,6
]}

Canevini, Maria Paola ^{[7
]}

Cantalupo, Gaetano ^{[8
]}

Cesaroni, Elisabetta ^{[9
]}

Contin, Manuela ^{[3
,10
]}

Coppola, Antonietta ^{[11
]}

Cordelli, Duccio Maria ^{[12
]}

Cricchiuti, Giovanni ^{[13
]}

De Giorgis, Valentina ^{[14
]}

De Leva, Maria Fulvia ^{[15
]}

De Rinaldis, Marta ^{[16
]}

d'Orsi, Giuseppe ^{[17
]}

Elia, Maurizio ^{[18
]}

Galimberti, Carlo Andrea ^{[19
]}

Morano, Alessandra ^{[20
]}

Granata, Tiziana ^{[21
]}

Guerrini, Renzo ^{[22
]}

Lodi, Monica A. M. ^{[23
]}

La Neve, Angela ^{[24
]}

Marchese, Francesca ^{[25
,26
]}

Masnada, Silvia ^{[27
]}

Michelucci, Roberto ^{[28
]}

Nosadini, Margherita ^{[29
]}

Pilolli, Nicola ^{[24
]}

Pruna, Dario ^{[30
]}

Ragona, Francesca ^{[21
]}

Rosati, Anna ^{[22
]}

Santucci, Margherita ^{[3
,6
]}

Spalice, Alberto ^{[31
]}

Pietrafusa, Nicola ^{[32
]}

Striano, Pasquale ^{[25
,26
]}

Tartara, Elena ^{[19
]}

Tassi, Laura ^{[33
]}

Papa, Amanda ^{[34
]}

Zucca, Claudio ^{[35
]}

Russo, Emilio ^{[1
]}

Mecarelli, Oriano ^{[36
]}

机构：

[1] Magna Graecia Univ Catanzaro, Sch Med, Sci Hlth Dept, Catanzaro, Italy

[2] Univ Cattolica Sacro Cuore, A Gemelli Univ Polyclin Fdn, Dept Woman & Child Hlth & Publ Hlth,Child Hlth Ar, Ist Ricovero & Cura Carattere Sci IRCCS,Pediat Ne, Rome, Italy

[3] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy

[4] Ist Ricovero & Cura Carattere Sci IRCCS, Ist Sci Neurol Bologna, Epilepsy Ctr, Reference Ctr Rare & Complex Epilepsies EpiCARE, Bologna, Italy

[5] Ist Ricovero & Cura Carattere Sci IRCCS Eugenio M, Sci Inst, Epilepsy & Clin Neurophysiol Unit, Treviso, Italy

[6] Ist Ricovero & Cura Carattere Sci IRCCS, Child Neuropsichiat, Ist Sci Neurol Bologna, Bologna, Italy

[7] Univ Milan, San Paolo Hosp, Dept Hlth Sci, Epilepsy Ctr, Milan, Italy

[8] Univ Verona, Dept Surg Sci Dent Gynecol & Pediat, Child Neuropsychiat, Verona, Italy

[9] Univ Ancona, Child Neurol & Psychiat Unit, G Salesi Childrens Hosp, Ancona, Italy

[10] Ist Ricovero & Cura Carattere Sci IRCCS, Ist Sci Neurol Bologna, Bologna, Italy

[11] Univ Naples Federico II, Epilepsy Ctr, Dept Neurosci Reprod & Odontostomatol Sci, Naples, Italy

[12] IRCCS Ist Sci Neurol Bologna, UOC Neuropsichiat Eta Pediat, Bologna, Italy

[13] Univ Hosp Udine, Inst Med, Dept Pediat, Epilepsy Ctr, Udine, Italy

[14] Ist Ricovero & Cura Carattere Sci IRCCS, Dept Child Neurol & Psychiat, Mondino Fdn, Pavia, Italy

[15] Santobono Pausilipon Childrens Hosp, Dept Neurosci, Pediat Neurol, Naples, Italy

[16] Ist Ricovero & Cura Carattere Sci IRCCS E Medea, Unit Severe Disabil Dev Age & Young Adults Dev Ne, Sci Inst, Brindisi, Italy

[17] Riuniti Hosp, Epilepsy Ctr, Clin Nervous Syst Dis, Foggia, Italy

[18] Ist Ricovero & Cura Carattere Sci IRCCS, Oasi Res Inst, Troina, Italy

[19] Ist Ricovero & Cura Carattere Sci IRCCS, Mondino Fdn, Epilepsy Ctr, Pavia, Italy

[20] Sapienza Univ, Dept Human Neurosci, Neurol Unit, Rome, Italy

[21] Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Ist Neurol Carlo Besta, Dept Pediat Neurosci, Milan, Italy

[22] A Meyer Childrens Hosp, Pediat Neurol Neurogenet & Neurobiol Unit & Labs, Florence, Italy

[23] Fatebenefratelli & Oftalmico Hosp, Dept Neurosci, Pediat Neurol Unit, Epilepsy Ctr, Milan, Italy

[24] Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy

[25] Ist Ricovero & Cura Carattere Sci IRCCS, Pediat Neurol & Muscular Dis Unit, G Gaslini Inst, Genoa, Italy

[26] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy

[27] V Buzzi Childrens Hosp, Dept Pediat Neurol, Milan, Italy

[28] Bellaria Hosp, Ist Ricovero & Cura Carattere Sci IRCCS, Unit Neurol, Ist Sci Neurol Bologna, Bologna, Italy

[29] Univ Hosp Padua, Dept Womens & Childrens Hlth, Paediat Neurol & Neurophysiol Unit, Padua, Italy

[30] Brotzu Hosp Trust, Pediat Neurol & Epileptol Unit, Cagliari, Italy

[31] Sapienza Univ Rome, Child Neurol Div, Dept Pediat, Rome, Italy

[32] Bambino Gesu Pediat Hosp, Dept Neurosci NS MT, Neurol Unit, Ist Ricovero & Cura Carattere Sci IRCCS, Rome, Italy

[33] Grande Osped Metropolitano Niguarda, Claudio Munari Epilepsy Surg Ctr, Azienda Socio Sanitaria Terr ASST, Milan, Italy

[34] Maggiore Carita Univ Hosp, Child Neuropsychiat Dept, Novara, Italy

[35] Ist Ricovero & Cura Carattere Sci IRCCS Eugenio M, Sci Inst, Clin Neurophysiol Unit, Lecce, Italy

[36] Sapienza Univ, Dept Human Neurosci, Rome, Italy

来源：

FRONTIERS IN NEUROLOGY | 2021年 / 12卷

关键词：

cannabidiol; epilepsy; Dravet syndrome; lennox-gastaut syndrome; expanded access program; OPEN-LABEL; EPILEPSY; CANNABINOIDS; CBD;

D O I：

10.3389/fneur.2021.673135

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Purified cannabidiol (CBD) was administered to highly refractory patients with Dravet (DS) or Lennox-Gastaut (LGS) syndromes in an ongoing expanded access program (EAP). Herein, we report interim results on CBD safety and seizure outcomes in patients treated for a 12-month period. Material and Methods: Thirty centers were enrolled from December 2018 to December 2019 within the open-label prospective EAP up to a maximum of 25 mg/kg per day. Adverse effects and liver function tests were assessed after 2 weeks; 1, 3, and 6 months of treatment; and periodically thereafter. Seizure endpoints were the percentage of patients with >= 50 and 100% reduction in seizures compared to baseline. Results: A total of 93 patients were enrolled and included in the safety analysis. Eighty-two patients [27 (32.9%) DS, 55 (67.1%) LGS] with at least 3 months of treatment have been included in the effectiveness analysis; median previously failed antiseizure medications was eight. Pediatric and adult patients were uniformly represented in the cohort. At 3-month follow-up, compared to the 28-day baseline period, the percentage of patients with at least a 50% reduction in seizure frequency was 40.2% (plus 1.2% seizure-free). Retention rate was similar according to diagnosis, while we found an increased number of patients remaining under treatment in the adult group. CBD was mostly coadministered with valproic acid (62.2%) and clobazam (41.5%). In the safety dataset, 29 (31.2%) dropped out: reasons were lack of efficacy [16 (17.2%)] and adverse events (AEs) [12 (12.9%)], and one met withdrawal criteria (1.1%). Most reported AEs were somnolence (22.6%) and diarrhea (11.9%), followed by transaminase elevation and loss of appetite. Conclusions: CBD is associated with improved seizure control also in a considerable proportion of highly refractory patients with DS and LGS independently from clobazam use. Overall, CBD safety and effectiveness are not dose-related in this cohort.

引用

页数：9

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